The mammalian growth factor TGFbeta negatively regulates cell proliferation in various systems. Here we provide evidence that another TGFbeta superfamily member, Drosophila Decapentaplegic (Dpp), stimulates cell proliferation. In the developing wing blade, somatic clones lacking the Dpp receptors Punt or Thick veins (Tkv), or lacking Schnurri, a transcription factor involved in Dpp signal interpretation, fail to grow when induced early in larval development. Furthermore the spatial requirement for these signaling components indicates that Dpp has to travel several cell diameters from its source in order to reach all cells that require its signal. The requirement for Tkv also depends on the distance of cells from the source of the Dpp signal. We propose that Dpp can act at a distance to positively control cell proliferation.

Reference

Reference
Arora
K.
,
Dai
H.
,
Kazuko
S. G.
,
Jamal
J.
,
O'Connor
M. B.
,
Letsou
A.
,
Warrior
R.
(
1995
)
The Drosophila schnurri gene acts in the Dpp/TGFsignaling pathway and encodes a transcription factor homologous to the human MBP family.
Cell
81
,
781
790
Basler
K.
,
Struhl
G.
(
1994
)
Compartment boundaries and the control of Drosophila limb pattern by hedgehog protein.
Nature
368
,
208
214
Brand
A. H.
,
Perrimon
N.
(
1993
)
Targeted gene expression as a means of altering cell fates and generating dominant phenotypes.
Development
118
,
401
415
Brummel
T. J.
,
Twombly
V.
,
Marques
G.
,
Wrana
J. L.
,
Newfeld
S. J.
,
Attisano
L.
,
Massague
J.
,
O'Connor
M. B.
,
Gelbart
W. M.
(
1994
)
Characterization and relationship of dpp receptors encoded by the saxophone and thick veins genes in Drosophila.
Cell
78
,
251
261
Campbell
G.
,
Weaver
T.
,
Tomlinson
A.
(
1993
)
Axis specification in the developing Drosophila appendage: the role of wingless, decapentaplegic, and the homeobox gene aristaless.
Cell
74
,
1113
1123
Capdevila
J.
,
Guerrero
I.
(
1994
)
Targeted expression of the signaling molecule decapentaplegic induces pattern duplications and growth alterations in Drosophila wings.
EMBO J
13
,
4459
4468
Crick
F. H. C.
,
Lawrence
P. A.
(
1975
)
Compartments and polyclones in insect development.
Science
189
,
340
347
Diaz-Benjumea
F. J.
,
Cohen
S. M.
(
1995
)
Serrate signals through Notch to establish a wingless-dependent organizer at the drosal/ventral compartment boundary of the Drosophila wing.
Development
121
,
4215
4225
Diaz-Benjumea
F. J.
,
Hafen
E.
(
1994
)
The sevenless signalling cassette mediates Drosophila EGF receptor function during epidermal development.
Development
120
,
569
578
Evan
G. I.
,
Lewis
G. K.
,
Ramsay
G.
,
Bishop
J. M.
(
1985
)
Isolation of monoclonal antibodies specific for human c-myc protooncogene product.
Mol. Cell. Biol
5
,
3610
3616
Ferguson
E. L.
,
Anderson
K. V.
(
1992
)
Decapentaplegic acts as a morphogen to organize dorsal-ventral pattern in the Drosophila embryo.
Cell
71
,
451
461
Garcia-Bellido
A.
(
1977
)
Inductive mechanisms in the process of wing vein formation in Drosophila.
Roux's Arch. Dev. Biol
182
,
93
106
Garcia-Bellido
A.
,
de Celis
J. F.
(
1992
)
Developmental genetics of the venation pattern of Drosophila.
Annu. Rev. Genet
26
,
277
304
Grieder
N. C.
,
Nellen
D.
,
Burke
R.
,
Basler
K.
,
Affolter
M.
(
1995
)
Schnurri is required for Drosophila dpp signaling and encodes a zinc finger protein similar to the mammalian transcription factor PRDII-BF1.
Cell
81
,
791
800
Letsou
A.
,
Arora
K.
,
Wrana
J. L.
,
Simin
K.
,
Twombly
V.
,
Jamal
J.
,
Staehling-Hampton
K.
,
Hoffmann
F. M.
,
Gelbart
W. M.
,
Massague
J.
,
O'Connor
M. B.
(
1995
)
Drosophila Dpp signaling is mediated by the punt gene product: a dual ligand-binding type II receptor of the TGFreceptor family.
Cell
80
,
899
908
Markowitz
S.
,
Wang
J.
,
Myeroff
L.
,
Parsons
R.
,
Sun
L.
,
Lutterbaugh
J.
,
Ran
R. S.
,
Zborowska
E.
,
Kinzler
K. W.
,
Vogelstein
B.
,
Brattain
M.
,
Willson
J. K. V.
(
1995
)
Inactivation of the type II TGFreceptor in colon cancer cells with microsatellite instability.
Science
268
,
1336
1338
Massague
J.
(
1990
)
The transforming growth factor-family.
Annu. Rev. Cell Biol
6
,
597
641
Masucci
J. D.
,
Miltenberger
R. J.
,
Hoffmann
F. M.
(
1990
)
Pattern-specific expression of the Drosophila decapentaplegic gene in imaginal disks is regulated by 3cis-regulatory elements.
Genes Dev
4
,
2011
2023
Nellen
D.
,
Affolter
M.
,
Basler
K.
(
1994
)
Receptor serine/threonine kinases implicated in the control of Drosophila body pattern by decapentaplegic.
Cell
78
,
225
237
Nellen
D.
,
Burke
R.
,
Struhl
G.
,
Basler
K.
(
1996
)
Direct and long-range action of a dpp morphogen gradient.
Cell
85
,
357
368
Padgett
R. W.
,
St Johnston
R. D.
,
Gelbart
W. M.
(
1987
)
A transcript from a Drosophila pattern gene predicts a protein homologous to the transforming growth factor-family.
Nature
325
,
81
84
Peifer
M.
,
Rauskolb
C.
,
Williams
M.
,
Riggleman
B.
,
Wieschaus
E.
(
1991
)
The segment polarity gene armadillo interacts with the winglesssignaling pathway in both embryonic and adult pattern formation.
Development
111
,
1029
1043
Penton
A.
,
Chen
Y.
,
Staehling-Hampton
K.
,
Wrana
J. L.
,
Attisano
L.
,
Szidonya
J.
,
Cassill
J. A.
,
Massague
J.
,
Hoffmann
F. M.
(
1994
)
Identification of two bone morphogenetic protein type I receptors in Drosophila and evidence that Brk25D is a decapentaplegic receptor.
Cell
78
,
239
250
Posakony
L. G.
,
Raftery
L. A.
,
Gelbart
W. M.
(
1991
)
Wing formation in Drosophila melanogaster requires decapentaplegic gene function along the anterior-posterior compartment boundary.
Mech. Dev
33
,
69
82
Reynisdottir
I.
,
Polyak
K.
,
Iavarone
A.
,
Massague
J.
(
1995
)
Kip/Cip and Ink4 Cdk inhibitors cooperate to induce cell cycle arrest in response to TGF.
Genes Dev
9
,
1831
1845
Ruberte
E.
,
Marty
T.
,
Nellen
D.
,
Affolter
M.
,
Basler
K.
(
1995
)
An absolute requirement for both the Type II and Type I receptors, punt and thick veins, for Dpp signaling in vivo.
Cell
80
,
890
898
Segal
D.
,
Gelbart
W. M.
(
1985
)
Shortvein, a new component of the decapentaplegic gene complex in Drosophila melanogaster.
Genetics
109
,
119
143
St Johnson
R. D.
,
Hoffmann
F. M.
,
Blackman
R. K.
,
Segal
D.
,
Grimaila
R.
,
Padgett
R. W.
,
Irick
H. A.
,
Gelbart
W. M.
(
1990
)
Molecular organization of the decapentaplegic gene in Drosophilamelanogaster.
Genes Dev
4
,
1114
1127
Staehling-Hampton
K.
,
Jackson
P. D.
,
Clark
M. J.
,
Brand
A. H.
,
Hoffmann
F. M.
(
1994
)
Specificity of bone morphogenetic protein-related factors: cell fate and gene expression changes in Drosophila embryos induced by decapentaplegic but not 60A.
Cell Growth Differ
5
,
585
593
Staehling-Hampton
K.
,
Laughon
A. S.
,
Hoffmann
F. M.
(
1995
)
A Drosophila protein related to the human zinc finger transcription factor PRDII/MBPI/HIV-EP1 is required for dpp signaling.
Development
121
,
3393
3403
Tabata
T.
,
Kornberg
T. B.
(
1994
)
Hedgehog is a signaling protein with a key role in patterning Drosophila imaginal discs.
Cell
76
,
89
102
Wharton
K. A.
,
Ray
R. P.
,
Gelbart
W. M.
(
1993
)
An activity gradient of decapentaplegic is necessary for the specification of dorsal pattern elements in the Drosophila embryo.
Development
117
,
807
822
Xu
T.
,
Rubin
G. M.
(
1993
)
Analysis of genetic mosaics in developing and adult Drosophila tissues.
Development
117
,
1223
1237
Zecca
M.
,
Basler
K.
,
Struhl
G.
(
1995
)
Sequential organizing activities of engrailed, hedgehog and decapentaplegic in the Drosophila wing.
Development
121
,
2265
2278
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